American pima cotton

151 men in Brazil, Nigeria, Kenya and China took 15 mg gossypol daily for 12 to 16 weeks, then were randomised to 7.5 or 10 mg daily for 40 weeks, against 51 controls. 81 reached spermatogenesis suppression. Potassium levels fluctuated within the normal range at these lower doses, FSH rose consistently and testicular volume fell before recovering. Recovery of fertility was the problem: 12 of 19 men on 7.5 mg recovered a sperm count above 20 million/mL within a year, but only 10 of 24 on 10 mg did, and 8 of 43 remained azoospermic one year after stopping. Every man with a varicocele failed to recover. This is the trial that fixes the irreversibility risk at roughly one in five and shows that recovery, unlike suppression, is dose- and concentration-dependent.

A randomised controlled study within the Chinese gossypol contraceptive programme tested whether potassium salt supplementation or the potassium-sparing agent triamterene could relieve gossypol-related hypokalaemia. Neither worked: potassium salt did not reverse the hypokalaemia, and triamterene neither prevented potassium loss nor enhanced retention. This is the study that converts gossypol hypokalaemia from a manageable adverse effect into a contraindication, because it demonstrates that the standard corrective measures fail.

Review of the animal toxicology and the human fertility-recovery data that led the WHO Special Programme of Research, Development and Research Training in Human Reproduction to decide that gossypol would not be acceptable as an antifertility drug. The authors draw the general lesson that contraceptive drugs must go through formal animal toxicology and phased clinical study. For a clinical reference database the operative point is that an international expert body reviewed the whole dataset and rejected the compound on safety grounds.

Seventeen phase I and II trials involving 759 patients were reviewed. Oral gossypol or AT-101 at 30 mg daily or lower was tolerable as monotherapy or with chemoradiation, with adverse events requiring strict monitoring and managed by dose reduction. Four randomised trials combined AT-101 with docetaxel-based regimens; benefit was seen in some high-risk subgroups rather than across the board. The review characterises a purified single enantiomer given under oncological supervision and does not support use of crude cotton preparations.

Both gossypol acetate enantiomers reduced uterine leiomyoma in rats, with the minus enantiomer better at improving pathology, suppressing oestrogen secretion and downregulating oestrogen receptor alpha and progesterone receptor. Both altered serum potassium; the plus enantiomer had the more marked effect on liver function. The paper states directly that hypokalaemia and mild liver function change are what limit the clinical application of the marketed gossypol acetate product in China.

Transcriptome comparison of four glanded and two glandless tetraploid cotton cultivars spanning Gossypium hirsutum and Gossypium barbadense, identifying a gene module and 29 hub genes associated with loss of gossypol and pigment glands. The practical significance for this record is that it confirms Gossypium barbadense as a gossypol-producing species and that gossypol content is determined by the glanded or glandless genotype of the cultivar, not by the species name alone.